Sivridis Efthimios, Giatromanolaki Alexandra, Koukourakis Michael I
Department of Pathology, Democritus University of Thrace, Alexandroupolis, Greece.
J Pathol. 2003 Oct;201(2):173-80. doi: 10.1002/path.1355.
It is becoming almost a dogma that tumours cannot grow beyond 1-2 mm(3) unless they are supported by a rich vascular supply 1. It is true that tumours promote angiogenesis and that highly vascularized carcinomas have, in general, a more aggressive clinical course than carcinomas of low vascularization 23. However, a study of intratumoral angiogenesis reveals that the newly formed vessels are commonly deprived of those structural qualities that would allow them to perform an optimal oxygenation function 3. Thus, most tumours, irrespective of their angiogenic status, behave as if they were 'hypoxic', urging (via angiogenic mediators) for, what would look paradoxical at first sight, more defective angiogenesis. It is hypothesized that tumour cells can grow into solid neoplasms by exploiting the host's pre-existing vessels, without the need for new blood vessel formation. Neovascularization, however, may be important for tumours with an exophytic pattern of growth as these, by their very nature, lose the host's sheltering stroma. Shifting to anaerobic glycolysis and activation of anti-apoptotic pathways are complementary mechanisms for tumour cell survival and growth. Besides, continuous and indiscriminate production of a defective vascular network ensures an increased metastatic potential since the newly formed intratumoral vessels, simulating venular-like spaces, are easily permeable to tumour cells, facilitating metastases.
几乎已成为一种定论的是，肿瘤若没有丰富的血管供应支持，就无法生长超过1 - 2毫米(3) 1。肿瘤确实会促进血管生成，而且一般来说，血管高度丰富的癌比血管化程度低的癌具有更具侵袭性的临床病程23。然而，一项关于肿瘤内血管生成的研究表明，新形成的血管通常缺乏那些能使其执行最佳氧合功能的结构特性3。因此，大多数肿瘤，无论其血管生成状态如何，其表现就好像处于“缺氧”状态，（通过血管生成介质）促使乍一看似乎矛盾的更多有缺陷的血管生成。据推测，肿瘤细胞可以通过利用宿主预先存在的血管生长为实体瘤，而无需形成新的血管。然而，新生血管形成对于具有外生性生长模式的肿瘤可能很重要，因为从其本质上讲，这些肿瘤会失去宿主的保护性基质。转向无氧糖酵解和激活抗凋亡途径是肿瘤细胞存活和生长的互补机制。此外，持续且无差别地生成有缺陷的血管网络会增加转移潜能，因为新形成的肿瘤内血管模拟静脉样空间，很容易让肿瘤细胞渗透，从而促进转移。
